Chronic Obstructive Pulmonary DiseasePhase 3NCT02796677

AMPLIFY - D6571C00001 Duaklir USA Phase III Study

A Phase 3 study testing Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg), Aclidinium bromide 400 μg (AB 400 μg) and Formoterol fumarate 12 μg (FF 12 μg) in people with Chronic Obstructive Pulmonary Disease, run by AstraZeneca at 163 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a multiple dose, randomized, parallel, double-blind, double-dummy, multicenter and multinational Phase III study to determine the efficacy and safety of Aclidinium bromide 400μg/Formoterol Fumarate (AB/FF) 12 μg compared to individual components and TIO (Tiotropium) 18 μg when administered to patients with… Read more about this study

Who is it for?: Ages 40 to 130 years
Conditions the study is for: Chronic Obstructive Pulmonary Disease
What is being tested?: Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg), Aclidinium bromide 400 μg (AB 400 μg) and Formoterol fumarate 12 μg (FF 12 μg)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,595 participants
Where: 163 sitesin 10 countries
Study dates: 5 Jul 2016to 8 Jun 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 130 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adult male or non-pregnant, non-lactating female patients aged ≥40.
Patients with diagnosis of moderate to very severe stable COPD: post-bronchodilator FEV1 < 80% of the predicted normal and post-bronchodilator FEV1/FVC < 70% at Screening Visit.
Symptomatic patients with a CAT score ≥10 at Screening and Randomization visit (Visits 1 and 2).
Current or former-smokers, with a smoking history of ≥ 10 pack-years.
Patients able to perform acceptable and repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005 criteria at Visit 1.
Patients eligible and able to participate in the study and who had signed an Informed Consent Form prior to initiation of any study-related procedures.

Who cannot join

Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff), or patients employed by or relatives of the employees of the site or sponsor.
Previous randomization in the present study D6571C00001.
Patients with predominant asthma.
Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening or during the run-in period.
Patients hospitalized for a COPD exacerbation (an emergency room visit for longer than 24 hours is considered a hospitalization) within 3 months prior to Screening Visit.
Clinically significant respiratory conditions other than COPD.

Show all 23Show fewer

Patients who in the Investigator's opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to Screening.
Use of long-term oxygen therapy (≥ 15 hours/day).
Patients who do not maintain regular day/night, waking/sleeping cycles including night shift workers.
Clinically significant cardiovascular conditions.
Patients with uncontrolled Type I or Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled hypertension.
Patients with history of long QT syndrome or whose QTc (calculated according to Fridericia's Formula QTc=QT/RR1/3) > 470 ms as indicated in the centralised reading report assessed at Screening.
Patients with clinically significant abnormalities in the laboratory tests, ECG parameters (other than QTc) or in the physical examination at Screening Visit that might comprise patient safety.
Patient with known non-controlled history of infection with human immunodeficiency virus and/or active hepatitis.
Patient with a history of hypersensitivity reaction to inhaled medication or any component thereof, including paradoxical bronchospasm.
Patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention or symptomatic non-stable prostate hypertrophy.
History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer.
Patients with any other serious or uncontrolled physical or mental dysfunction.
Patients with a history (within 2 years prior to screening) of drug and/or alcohol abuse that may prevent study compliance based on the Investigator judgment.
Patients unlikely to be cooperative or that cannot comply with the study procedures.
Patients treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to Screening.
Patients who intended to use any concomitant medication not permitted by this protocol or who had not undergone the required washout period for a particular prohibited medication.
Patients unable to give consent, or patients of consenting age but under guardianship, or vulnerable patients. Patients who demonstrate < 80% compliance with the electronic diary during the run-in period.

Trial locations and contacts

163 sites in 10 countries.

Country

City, postcode or hospital

163 sites in 10 countries

United States85 sites

Research Site
Abingdon, Virginia, 24210
Research Site
Altoona, Pennsylvania, 16602
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Arlington, Texas, 76012
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Baytown, Texas, 77521
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Blue Ridge, Georgia, 30513
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Boerne, Texas, 78006
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Brooklyn, New York, 11230
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Buffalo, New York, 14215
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Canton, Ohio, 44718
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Charlotte, North Carolina, 28207
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Charlotte, North Carolina, 28277
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Chelsea, Michigan, 48118
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Chicago, Illinois, 60602
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Cincinnati, Ohio, 45231
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Cincinnati, Ohio, 45242
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Cincinnati, Ohio, 45246
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Clearwater, Florida, 33765
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Columbia, South Carolina, 29204
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Columbus, Ohio, 43207
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Columbus, Ohio, 43215
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Corona, California, 92879
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Dallas, Texas, 75225
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Dublin, Ohio, 43016
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East Providence, Rhode Island, 02914
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Edgewater, Florida, 32132
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Edina, Minnesota, 55435
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Edmond, Oklahoma, 73034
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Fall River, Massachusetts, 02720
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Farmington Hills, Michigan, 48336
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Fort Worth, Texas, 76104
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Fremont, Nebraska, 68025
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Fresno, California, 93702
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Fridley, Minnesota, 55432
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Fullerton, California, 92835
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Gaffney, South Carolina, 29340
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Gastonia, North Carolina, 28054
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Grove City, Ohio, 43123
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Gulf Shores, Alabama, 36542
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Hollywood, Florida, 33021
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Homestead, Florida, 33030
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Houston, Texas, 77074
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Lafayette, Louisiana, 70508
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Las Vegas, Nevada, 89102
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Lewisville, Texas, 75067
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Lincoln, California, 95648
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McKinney, Texas, 75069
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Medford, Oregon, 97504
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Miami, Florida, 33144
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Miami, Florida, 33186
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Miami Lakes, Florida, 33016
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Midvale, Utah, 84047
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Midwest City, Oklahoma, 73110
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Minneapolis, Minnesota, 55407
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Mt. Pleasant, South Carolina, 29464
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New York, New York, 10036
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Newport News, Virginia, 23606
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Oklahoma City, Oklahoma, 73104
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Omaha, Nebraska, 68114
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Omaha, Nebraska, 68134
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Ormond Beach, Florida, 32174
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Phoenix, Arizona, 85018
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Pittsburgh, Pennsylvania, 15243
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Port Orange, Florida, 32129
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Portage, Indiana, 46368
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Rochester, New York, 14618
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Saint Charles, Missouri, 63301
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San Diego, California, 92120
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Sarasota, Florida, 34233
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Spartanburg, South Carolina, 29303
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St Louis, Missouri, 63117
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St Louis, Missouri, 63141
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St. Petersburg, Florida, 33704
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St. Petersburg, Florida, 33709
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Tampa, Florida, 33603
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The Bronx, New York, 10455
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Tomball, Texas, 77375
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Troy, Michigan, 48085
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Tucson, Arizona, 85712
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Union, South Carolina, 29379
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Waterbury, Connecticut, 06708
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Wilmington, North Carolina, 28401
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Winter Park, Florida, 32789
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Woodbury, Minnesota, 55125
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Woodstock, Georgia, 30189
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Wyomissing, Pennsylvania, 19610

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Germany20 sites

Research Site
Berlin, 10117
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Berlin, 10629
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Berlin, 10717
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Berlin, 10787
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Berlin, 12627
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Bochum, 44787
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Dortmund, 44263
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Dresden, 01069
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Frankfurt, 60596
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Großhansdorf, 20927
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Hamburg, 20253
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Hamburg, 20354
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Hamburg, D-22143
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Hanover, 30159
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Leipzig, 04103
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Leipzig, 04275
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Lübeck, 23552
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Marburg, 35037
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München, 80539
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Schwerin, 19055

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Poland12 sites

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Bialystok, 15-003
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Częstochowa, 42-200
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Gdansk, 80-382
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Gdynia, 81-384
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Inowrocław, 88-100
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Katowice, 40-040
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Ostrowiec Świętokrzyski, 27-400
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Pabianice, 95-200
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Szczecin, 70-111
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Warsaw, 01-192
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Wroclaw, 50-088
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Zabrze, 41-800

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Bulgaria10 sites

Research Site
Dimitrovgrad, 6400
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Gabrovo, 5300
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Roman, 3130
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Rousse, 7002
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Sevlievo, 5400
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Sliven, 8800
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Sofia, 1002
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Sofia, 1431
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Stara Zagora, 6003
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Vidin, 3700

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Hungary9 sites

Research Site
Balassagyarmat, 2660
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Budapest, 1036
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Debrecen, 4031
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Gödöllő, 2100
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Komló, 7300
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Nyíregyháza, 4400
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Pécs, 7635
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Szigetszentmiklós, 2310
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Szombathely, 9700

Other trials in Hungary

Ukraine9 sites

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Ivano-Frankivsk, 76012
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Kharkiv, 61035
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Kharkiv, 61039
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Odesa, 65009
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Poltava, 36024
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Sumy, 40030
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Uzhhorod, 88017
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Vinnytsia, 21018
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Zhytomyr, 10002

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United Kingdom7 sites

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Birmingham, B15 2SQ
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Cardiff, CF14 5GJ
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Chorley, PR7 7NA
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Glasgow, G20 OSP
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Hexham, NE46 1QJ
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Liverpool, L22 0LG
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Manchester, M15 6SX

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Czechia5 sites

Research Site
Jaroměř, 544 01
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Jindřichův Hradec, 377 01
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Prague, 182 00
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Rokycany, 33722
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Strakonice, 38601

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Israel3 sites

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Jerusalem, 91120
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Petah Tikva, 49100
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Rehovot, 76100

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Spain3 sites

Research Site
Alicante, 03004
Research Site
Barcelona, 08830
Research Site
Lleida, 25198

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About this study

Official title: A 24 Week Treatment, Multicenter, Randomized, Double Blinded, Double Dummy, Parallel-group, Clinical Trial Evaluating the Efficacy and Safety of Aclidinium Bromide 400 μg/Formoterol Fumarate 12 μg Fixed-dose Combination BID Compared With Each Monotherapy (Aclidinium Bromide 400 μg BID and Formoterol Fumarate 12 μg BID) and Tiotropium 18 μg QD When Administered to Patients With Stable Chronic Obstructive Pulmonary Disease.

Read the detailed description

This study was conducted to assess the bronchodilator efficacy and safety as well as effect on health related quality of life of AB/FF 400/12 μg compared to the individual components (AB 400 μg and FF 12 μg) in COPD patients. The trial duration of 24 weeks allows the assessment of the effect on symptoms improvement of the combined treatments versus individual components as well as the long term bronchodilation comparison between AB 400 μg and TIO 18 μg in minimizing the risk of COPD exacerbations in current or former smokers, aged ≥40 in symptomatic COPD patients.

Conditions: Chronic Obstructive Pulmonary Disease
Being tested: Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg), Aclidinium bromide 400 μg (AB 400 μg), Formoterol fumarate 12 μg (FF 12 μg), Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg, Tiotropium 18 μg (TIO 18 μg)
Keywords: Safety, Efficacy, Aclidinium bromide, Formoterol fumarate, Tiotropium, Bronchodilation, COPD
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg)Drug
Also called Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)
Inhalation powder
Aclidinium bromide 400 μg (AB 400 μg)Drug
Also called Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)
Inhalation powder
Formoterol fumarate 12 μg (FF 12 μg)Drug
Also called Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)
Inhalation powder
Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μgOther
Also called Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)
Inhalation powder
Tiotropium 18 μg (TIO 18 μg)Drug
Also called Oral Inhalation (by Handihaler® Dry Powder Inhaler, DPI)
Powder in capsules for oral inhalation
Placebo to TIO 18 μgOther
Also called Oral Inhalation (by Handihaler® Dry Powder Inhaler, DPI)
Powder in capsules for oral inhalation

Study groups in NCT02796677
Study group	Role	What they receive
AB/FF 400/12 μg BID	Experimental	Participants were administered AB/FF 400/12 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment. Receives: Drug: Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg); Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg
AB 400 μg BID	Experimental	Participants were administered AB 400 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment. Receives: Drug: Aclidinium bromide 400 μg (AB 400 μg); Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg
FF 12 μg BID	Experimental	Participants were administered FF 12 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment. Receives: Drug: Formoterol fumarate 12 μg (FF 12 μg); Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg
TIO 18 μg QD	Experimental	Participants were administered TIO 18 μg via Handihaler® inhale once daily for 24 weeks of treatment. Receives: Drug: Tiotropium 18 μg (TIO 18 μg); Other: Placebo to TIO 18 μg

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in 1-hour Morning Post-dose Dose Forced Expiratory Volume in 1 Second (FEV1) of AB/FF 400/12 μg Compared to AB 400 μg at Week 24
To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 at 1 hour post-dose of AB/FF 400/12 µg compared to AB 400 μg after administration of oral inhalation powder BID via DIP to participants with COPD.
Baseline was defined as the average of the two FEV1 values measured just prior to the administration of the first dose of investigational product (IP) at randomization Visit. If one of the two was missing, then the available one would be used as baseline value.
Measured: At baseline 1-hour postdose and Week 24
Change From Baseline in Morning Predose (Trough) FEV1 of AB/FF 400/12 μg Compared to FF 12 μg at Week 24
To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough) of AB/FF 400/12 µg compared to FF 12 μg after administration of oral inhalation powder BID via DPI to participants with COPD.
Morning pre-dose (trough) FEV1 was defined as the average of the corresponding -30 minute and 0 minute before the morning study medication at Week 24. If one time-point was missing then the available one would be used as morning pre-dose.
Measured: At baseline morning predose and Week 24
Change From Baseline in Morning Predose (Trough) FEV1 at Week 24 Comparing AB 400 μg Versus TIO 18 μg to Demonstrate Non-inferiority
To assess the non-inferior bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough)of AB 400 µg compared to TIO 18 μg after administration of oral inhalation powder BID via DPI to participants with COPD.
Measured: At baseline morning predose and Week 24

Secondary outcomes (2)

Change From Baseline in Normalized Area Under Curve 3hours Post-dose (nAUC0-3/3h) FEV1 of AB/FF 400/12 μg Compared to AB 400 μg and and FF 12 μg at Week 24
To assess the bronchodilatory effect by evaluating the mean changes from baseline in nAUC0-3/3h FEV1 of AB/FF 400/12 µg compared to AB 400 μg and and FF 12 μg after administration of oral inhalation powder BID via DPI to participants with COPD.
Measured: At Day 1 and Day 169
Responder (Number of Participants) Analysis of St. George's Respiratory Questionnaire (SGRQ) Total Score With AB/FF 400/12 μg Versus AB 400 μg and FF 12 μg.
SGRQ was a A standardized self-completed tool used to measure impaired health and perceived well-being ("quality of life") in respiratory diseases. The questionnaire contained 50 items divided into 3 (symptoms, activity and impacts) dimensions. Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100%, zero score indicating no impairment of life quality. A summary score utilizing responses to all items is the total SGRQ score which also ranges from 0 to 100%. The SGRQ scores are calculated using weights attached to each item of the questionnaire which provides an estimate of the distress associated with the symptoms or state described in each item. Higher scores indicate poorer health. A decrease of at least 4 units in the SGRQ total score has been established as the criterion for minimal meaningful improvement. SGRQ responders will be those with a decrease in SGRQ total score of at least 4 units from baseline.
Measured: At baseline and Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jul 20168 Jun 2017

First posted13 Jun 2016 (estimated)
Study start5 Jul 2016
Primary completion8 Jun 2017
Study completion8 Jun 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 1,595 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02796677
Sponsor's protocol ID: D6571C00001
Status last verified: Nov 2018
First submitted: 31 May 2016
Last updated: 9 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: Yes

Publications

Sethi S, Kerwin E, Watz H, Ferguson GT, Mroz RM, Segarra R, Molins E, Jarreta D, Garcia Gil E. AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD. Int J Chron Obstruct Pulmon Dis. 2019 Mar 22;14:667-682. doi: 10.2147/COPD.S189138. eCollection 2019.
PubMed 30962681

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 24 Week Treatment, Multicenter, Randomized, Double Blinded, Double Dummy, Parallel-group, Clinical Trial Evaluating the Efficacy and Safety of Aclidinium Bromide 400 μg/Formoterol Fumarate 12 μg Fixed-dose Combination BID Compared With Each Monotherapy (Aclidinium Bromide 400 μg BID and Formoterol Fumarate 12 μg BID) and Tiotropium 18 μg QD When Administered to Patients With Stable Chronic Obstructive Pulmonary Disease.
ClinicalTrials.gov ID: NCT02796677
Acronym / sponsor ID: D6571C00001
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Safety, Efficacy, Aclidinium bromide, Formoterol fumarate, Tiotropium, Bronchodilation, COPD
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,595 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 5 Jul 2016 (actual)
Primary completion: 8 Jun 2017 (actual)
Study completion: 8 Jun 2017 (actual)
First posted: 13 Jun 2016 (estimated)
Results: Posted 9 Nov 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
AB/FF 400/12 μg BID	Experimental	Drug: Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg), Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μgParticipants were administered AB/FF 400/12 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment.
AB 400 μg BID	Experimental	Drug: Aclidinium bromide 400 μg (AB 400 μg), Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μgParticipants were administered AB 400 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment.
FF 12 μg BID	Experimental	Drug: Formoterol fumarate 12 μg (FF 12 μg), Other: Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μgParticipants were administered FF 12 μg via Pressair®/Genuair® inhaler twice daily for 24 weeks of treatment.
TIO 18 μg QD	Experimental	Drug: Tiotropium 18 μg (TIO 18 μg), Other: Placebo to TIO 18 μgParticipants were administered TIO 18 μg via Handihaler® inhale once daily for 24 weeks of treatment.

Who may qualify

Ages: 40 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Adult male or non-pregnant, non-lactating female patients aged ≥40.
Patients with diagnosis of moderate to very severe stable COPD: post-bronchodilator FEV1 < 80% of the predicted normal and post-bronchodilator FEV1/FVC < 70% at Screening Visit.
Symptomatic patients with a CAT score ≥10 at Screening and Randomization visit (Visits 1 and 2).
Current or former-smokers, with a smoking history of ≥ 10 pack-years.
Patients able to perform acceptable and repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005 criteria at Visit 1.

Key exclusion criteria (23 listed)

Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff), or patients employed by or relatives of the employees of the site or sponsor.
Previous randomization in the present study D6571C00001.
Patients with predominant asthma.
Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening or during the run-in period.
Patients hospitalized for a COPD exacerbation (an emergency room visit for longer than 24 hours is considered a hospitalization) within 3 months prior to Screening Visit.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg)Also: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)Inhalation powder	Drug	AB/FF 400/12 μg BID
Aclidinium bromide 400 μg (AB 400 μg)Also: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)Inhalation powder	Drug	AB 400 μg BID
Formoterol fumarate 12 μg (FF 12 μg)Also: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)Inhalation powder	Drug	FF 12 μg BID
Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μgAlso: Oral Inhalation (by Pressair®/Genuair® Dry Powder Inhaler)Inhalation powder	Other	AB 400 μg BID, AB/FF 400/12 μg BID, FF 12 μg BID
Tiotropium 18 μg (TIO 18 μg)Also: Oral Inhalation (by Handihaler® Dry Powder Inhaler, DPI)Powder in capsules for oral inhalation	Drug	TIO 18 μg QD
Placebo to TIO 18 μgAlso: Oral Inhalation (by Handihaler® Dry Powder Inhaler, DPI)Powder in capsules for oral inhalation	Other	TIO 18 μg QD

Primary outcome

Change From Baseline in 1-hour Morning Post-dose Dose Forced Expiratory Volume in 1 Second (FEV1) of AB/FF 400/12 μg Compared to AB 400 μg at Week 24
Time frame: At baseline 1-hour postdose and Week 24
To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 at 1 hour post-dose of AB/FF 400/12 µg compared to AB 400 μg after administration of oral inhalation powder BID via DIP to participants with COPD. Baseline was defined as the average of the two FEV1 values measured just prior to the administration of the first dose of investigational product (IP) at randomization Visit. If one of the two was missing, then the available one would be used as baseline value.
Change From Baseline in Morning Predose (Trough) FEV1 of AB/FF 400/12 μg Compared to FF 12 μg at Week 24
Time frame: At baseline morning predose and Week 24
To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough) of AB/FF 400/12 µg compared to FF 12 μg after administration of oral inhalation powder BID via DPI to participants with COPD. Morning pre-dose (trough) FEV1 was defined as the average of the corresponding -30 minute and 0 minute before the morning study medication at Week 24. If one time-point was missing then the available one would be used as morning pre-dose.
Change From Baseline in Morning Predose (Trough) FEV1 at Week 24 Comparing AB 400 μg Versus TIO 18 μg to Demonstrate Non-inferiority
Time frame: At baseline morning predose and Week 24
To assess the non-inferior bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough)of AB 400 µg compared to TIO 18 μg after administration of oral inhalation powder BID via DPI to participants with COPD.

2 secondary outcomes

Change From Baseline in Normalized Area Under Curve 3hours Post-dose (nAUC0-3/3h) FEV1 of AB/FF 400/12 μg Compared to AB 400 μg and and FF 12 μg at Week 24
Time frame: At Day 1 and Day 169
Responder (Number of Participants) Analysis of St. George's Respiratory Questionnaire (SGRQ) Total Score With AB/FF 400/12 μg Versus AB 400 μg and FF 12 μg.
Time frame: At baseline and Week 24

Results and safety

Results posted to the registry on 9 Nov 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aclidinium Bromide (AB)/Formoterol Fumarate (FF) 400/12 μg	317	279
AB 400 μg	478	405
FF 12 μg	320	267
Tiotropium (TIO) 18 μg	479	405

Primary outcome: Change From Baseline in 1-hour Morning Post-dose Dose Forced Expiratory Volume in 1 Second (FEV1) of AB/FF 400/12 μg Compared to AB 400 μg at Week 24

Time frame: At baseline 1-hour postdose and Week 24. Least squares mean (Standard Error). Unit: Litres

Measure	AB/FF 400/12 μg n = 314	AB 400 μg n = 475	FF 12 μg n = 319	TIO 18 μg n = 475
Value	0.253 (0.013)	0.169 (0.011)	0.168 (0.013)	0.161 (0.011)

AB/FF 400/12 μg vs AB 400 μg: LS mean difference: 0.084 (95% CI 0.051 to 0.117), p <0.0001, Mixed model for repeated measures

Population analysed: Intention-to Treat (ITT) population: All randomized participants who took at least one dose of IP and had at least a baseline FEV1, under the ITT principle and regardless the adherence to the randomized treatment.

Primary outcome: Change From Baseline in Morning Predose (Trough) FEV1 of AB/FF 400/12 μg Compared to FF 12 μg at Week 24

Time frame: At baseline morning predose and Week 24. Least squares mean (Standard Error). Unit: Litres

Measure	AB/FF 400/12 μg n = 314	AB 400 μg n = 475	FF 12 μg n = 319	TIO 18 μg n = 475
Value	0.080 (0.014)	0.066 (0.012)	0.025 (0.014)	0.060 (0.012)

AB/FF 400/12 μg vs FF 12 μg: LS mean difference: 0.055 (95% CI 0.023 to 0.088), p = 0.0009, Mixed model for repeated measures

Population analysed: ITT population: All randomized participants who took at least one dose of IP and had at least a baseline FEV1, under the ITT principle and regardless the adherence to the randomized treatment.

Primary outcome: Change From Baseline in Morning Predose (Trough) FEV1 at Week 24 Comparing AB 400 μg Versus TIO 18 μg to Demonstrate Non-inferiority

Time frame: At baseline morning predose and Week 24. Least squares mean (Standard Error). Unit: Litres

Measure	AB 400 μg n = 423	TIO 18 μg n = 419
Value	0.064 (0.013)	0.057 (0.013)

AB 400 μg vs TIO 18 μg: LS mean difference: 0.007 (95% CI -0.021 to 0.035), p = 0.6377, Mixed model for repeated measures

Population analysed: Per-Protocol (PP) population: A subset of the ITT population, consisted of participants who met all inclusion/exclusion criteria liable to affect the efficacy assessment, had sufficient treatment compliance, and did not present serious deviations of the protocol that might affect efficacy.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration). Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AB/FF 400/12 μg	23 of 314 (7.3%)	173 of 314 (55.1%)	1 of 314
AB 400 μg	41 of 475 (8.6%)	222 of 475 (46.7%)	1 of 475
FF 12 μg	22 of 319 (6.9%)	178 of 319 (55.8%)	4 of 319
TIO 18 μg	37 of 475 (7.8%)	241 of 475 (50.7%)	2 of 475

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30962681Sethi S, Kerwin E, Watz H, Ferguson GT, Mroz RM, Segarra R, Molins E, Jarreta D, Garcia Gil E. AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD. Int J Chron Obstruct Pulmon Dis. 2019 Mar 22;14:667-682. doi: 10.2147/COPD.S189138. eCollection 2019.
ProtocolLink provided by the sponsor.
SAPLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sanjay Sethi principal investigator

3495 Bailey Ave , Buffalo NY14215, USA

163 sites in 10 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 163 sites in United States, Germany, Poland, Bulgaria, Hungary and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in 1-hour Morning Post-dose Dose Forced Expiratory Volume in 1 Second (FEV1) of AB/FF 400/12 μg Compared to AB 400 μg at Week 24 (time frame: At baseline 1-hour postdose and Week 24). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02796677, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2018.